In Vivo Porcine Model of Acute Iliocaval Deep Vein Thrombosis.

CLINICAL IMPACT: The study establishes a rapid, technically straightforward, and reproducible porcine large animal model for acute iliocaval deep vein thrombosis (DVT). The procedure can be performed with basic endovascular skillsets. With its procedural efficiency and consistency, the platform is promising for comparative in vivo testing of venous thrombectomy devices in a living host, and for future verification and validation studies to determine efficacy of novel thrombectomy devices relative to predicates.

Multimodal thrombectomy device for treatment of acute deep venous thrombosis.

Deep vein thrombosis (DVT) is a potentially deadly medical condition that is costly to treat and impacts thousands of Americans every year. DVT is characterized by the formation of blood clots within the deep venous system of the body. If a DVT dislodges it can lead to venous thromboembolism (VTE) and pulmonary embolism (PE), both of which can lead to significant morbidity or death. Current treatment options for DVT are limited in both effectiveness and safety, in part because the treatment of the DVT cannot be confined to a defined sequestered treatment zone. We therefore developed and tested a novel thrombectomy device that enables the sequesteration of a DVT to a defined treatment zone during fragmentation and evacuation. We observed that, compared to a predicate thrombectomy device, the sequestered approach reduced distal DVT embolization during ex vivo thrombectomy. The sequestered approach also facilitated isovolumetric infusion and suction that enabled clearance of the sequestered treatment zone without significantly impacting vein wall diameter. Results suggest that our novel device using sequestered therapy holds promise for the treatment of high risk large-volume DVTs.

Patient-derived small intestinal myofibroblasts direct perfused, physiologically responsive capillary development in a microfluidic Gut-on-a-Chip Model.

The development and physiologic role of small intestine (SI) vasculature is poorly studied. This is partly due to a lack of targetable, organ-specific markers for in vivo studies of two critical tissue components: endothelium and stroma. This challenge is exacerbated by limitations of traditional cell culture techniques, which fail to recapitulate mechanobiologic stimuli known to affect vessel development. Here, we construct and characterize a 3D in vitro microfluidic model that supports the growth of patient-derived intestinal subepithelial myofibroblasts (ISEMFs) and endothelial cells (ECs) into perfused capillary networks. We report how ISEMF and EC-derived vasculature responds to physiologic parameters such as oxygen tension, cell density, growth factors, and pharmacotherapy with an antineoplastic agent (Erlotinib). Finally, we demonstrate effects of ISEMF and EC co-culture on patient-derived human intestinal epithelial cells (HIECs), and incorporate perfused vasculature into a gut-on-a-chip (GOC) model that includes HIECs. Overall, we demonstrate that ISEMFs possess angiogenic properties as evidenced by their ability to reliably, reproducibly, and quantifiably facilitate development of perfused vasculature in a microfluidic system. We furthermore demonstrate the feasibility of including perfused vasculature, including ISEMFs, as critical components of a novel, patient-derived, GOC system with translational relevance as a platform for precision and personalized medicine research.

Identification of multiple genetic loci in the mouse controlling immobility time in the tail suspension and forced swimming tests.

Depression is one of the most famous psychiatric disorders in humans in all over the countries and considered a complex neurobehavioral trait and difficult to identify causal genes. Tail suspension test (TST) and forced swimming test (FST) are widely used for assessing depression-like behavior and antidepressant activity in mice. A variety of antidepressant agents are known to reduce immobility time in both TST and FST. To identify genetic determinants of immobility duration in both tests, we analyzed 101 F2 mice from an intercross between C57BL/6 and DBA/2 strains. Quantitative trait locus (QTL) mapping using 106 microsatellite markers revealed three loci (two significant and one suggestive) and five suggestive loci controlling immobility time in the TST and FST, respectively. Results of QTL analysis suggest a broad description of the genetic architecture underlying depression, providing underpinnings for identifying novel molecular targets for antidepressants to clear the complex genetic mechanisms of depressive disorders.

The effects of enriching laboratory cages using various physical structures on multiple measures of welfare in singly-housed rats.

The single housing of laboratory rats may be recommended in some situations such as hypothesis-driven or test-specific studies, during electroencephalogram recording of phases of sleep and after surgical procedures. However, as single housing of laboratory rats has been shown to be stressful, modification of the housing environment is needed to improve the welfare of these animals. This experiment was carried out to investigate the long-term effects of environmental enrichment on some behavioural, physiological, pathological and psychological measures of welfare. With two batches of animals, 24 rats were housed singly in either enriched cages (EC) (n = 12 cages) or unenriched cages (UC) (n = 12 cages). Behaviour was sampled every week and so was body weight and weight gain over a six-week observation period. Behaviours of the rats in the elevated plus-maze were recorded on the seventh week, whereas organ weights were recorded postmortem. The results revealed that long-term single housing of rats in super-enriched cages increased levels of indicators of good welfare including sleep, exploration, movement and feeding behaviour, body weights, weight gains and the relative weights of the thymus gland and spleen, and decreased levels of indicators of poor welfare such as stationary behaviour and the relative weight of adrenal glands. Thus, enrichment of conventional cages of newly weaned singly-housed laboratory rats with multiple physical structures appeared to improve their ability to control the environment and to promote their species-specific behaviour; changes that can ultimately result in good welfare.

The effects of cage enrichment on agonistic behaviour and dominance in male laboratory rats (Rattus norvegicus).

This experiment was carried out to investigate the effects of enriching laboratory cages on agonistic interaction and dominance of rats. In a series of three replicates, 48 rats were housed in groups of four in either 'standard' or 'enriched' cages for 6 weeks. Successful aggressive and defensive behaviour that ended up in a clear winner and loser were sampled in the first hour of the dark phase of the light/dark cycle every other week. Rats in the 'complex' cages showed lower levels of both successful aggressive and successful defensive bouts compared to rats in the 'standard' cages. Enriching cages of laboratory rat did not change the social order of the animals in the cage. Thus, enhancing the complexity of cages of laboratory rats by the particular cage modification regimen implemented in this experiment could be considered enrichment and could therefore result in an improvement of welfare in these animals.

The effects of enhancing cage complexity on the behaviour and welfare of laboratory rats.

This experiment was carried out to investigate the long-term effects of enhancing cage complexity on behavioural measures of welfare in laboratory rats. We housed 72 rats in groups of four in either 'enriched' or 'unenriched' cages for six weeks. Scan and focal animal sampling were conducted in both the light and dark phase of the second, fourth and sixth weeks. Results revealed that rats in the 'enriched' cages showed longer durations of sleep behaviour, and low levels of agonistic behaviour compared to rats in the 'unenriched' cages. Results importantly demonstrated that the behavioural changes observed in the enriched environment were due to the presence of the enrichments themselves in the cages (indirect effects) and not due merely to rats interacting with the enrichment items in their environment. Thus, enhancing the complexity of conventional laboratory cages can promote behaviour such as longer bouts of sleep that is likely to be indicative of good welfare, and diminish levels of behaviour such as aggression that is likely to lead to poor welfare.